Abstract:
:A high throughput method was developed and validated for the quantitative determination of LAG078, a lipid-lowering compound, in dog plasma obtained during toxicokinetic studies. The method was based on reverse phase liquid chromatographic separation of the analyte from plasma extract followed by turbo-ionspray (TIS) in the negative ion mode and tandem mass spectrometry in the multiple reaction monitoring (MRM) mode. Extraction was performed using a combination of protein precipitation and liquid-liquid extraction in the 96-well plate format to increase the throughput of the method. Optimized chromatographic separation under basic condition (pH approximately 10) in a short polymer based column (50 mm x 2.0 mm i.d.) coupled with MRM mode of detection yielded clean chromatograms with minimal signal suppression. The standard curve was linear (r = 0.997) within the concentration range of 0.05 (lower limit of quantification; LLOQ) to 50 ng/ml using only 0.1 ml of dog plasma. The accuracy of the method varied from 95 to 100% with a precision (CV) of 3.04-10.8% over the concentration range. The method was simple, rapid, and robust.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Majumdar TK,Wu S,Vedananda S,Tse FLdoi
10.1016/j.jpba.2004.02.020subject
Has Abstractpub_date
2004-06-29 00:00:00pages
853-66issue
4eissn
0731-7085issn
1873-264Xpii
S0731708504001062journal_volume
35pub_type
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